INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells

Show full item record

Bookmark or cite this item: http://hdl.handle.net/10027/7725

Files in this item

File Description Format
PDF 1471-2407-10-647.pdf (4MB) (no description provided) PDF
Title: Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells
Author(s): Raghu, Hari; Sodadasu, Prasanna Kumar; Malla, Rama Rao; Gondi, Christopher S.; Estes, Norman; Rao, Jasti S.
Subject(s): breast cancer lipid rafts
Abstract: Background uPAR and MMP-9, which play critical roles in tumor cell invasion, migration and angiogenesis, have been shown to be associated with lipid rafts. Methods To investigate whether cholesterol could regulate uPAR and MMP-9 in breast carcinoma, we used MβCD (methyl beta cyclodextrin, which extracts cholesterol from lipid rafts) to disrupt lipid rafts and studied its effect on breast cancer cell migration, invasion, angiogenesis and signaling. Results Morphological evidence showed the association of uPAR with lipid rafts in breast carcinoma cells. MβCD treatment significantly reduced the colocalization of uPAR and MMP-9 with lipid raft markers and also significantly reduced uPAR and MMP-9 at both the protein and mRNA levels. Spheroid migration and invasion assays showed inhibition of breast carcinoma cell migration and invasion after MβCD treatment. In vitro angiogenesis studies showed a significant decrease in the angiogenic potential of cells pretreated with MβCD. MβCD treatment significantly reduced the levels of MMP-9 and uPAR in raft fractions of MDA-MB-231 and ZR 751 cells. Phosphorylated forms of Src, FAK, Cav, Akt and ERK were significantly inhibited upon MβCD treatment. Increased levels of soluble uPAR were observed upon MβCD treatment. Cholesterol supplementation restored uPAR expression to basal levels in breast carcinoma cell lines. Increased colocalization of uPAR with the lysosomal marker LAMP1 was observed in MβCD-treated cells when compared with untreated cells. Conclusion Taken together, our results suggest that cholesterol levels in lipid rafts are critical for the migration, invasion, and angiogenesis of breast carcinoma cells and could be a critical regulatory factor in these cancer cell processes mediated by uPAR and MMP-9.
Issue Date: 2010-11-24
Publisher: BioMed Central
Citation Info: Raghu, H., Sodadasu, P. K., Malla, R. R., Gondi, C. S., Estes, N., & Rao, J. S. 2010. Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells. BMC Cancer, 10:647. DOI: 10.1186/1471-2407-10-647
Type: Article
Description: © 2010 Raghu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/2.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: 10.1186/1471-2407-10-647
URI: http://hdl.handle.net/10027/7725
ISSN: 1471-2407
Date Available in INDIGO: 2011-05-27
 

This item appears in the following Collection(s)

Show full item record

Statistics

Country Code Views
United States of America 197
China 36
United Kingdom 15
Germany 6
Netherlands 4

Browse

My Account

Information

Access Key